The PT is not sensitive to deficiencies of coagulation factors VIII, IX, XI, XII ("intrinsic pathway" factors), or factor XIII, although the TF/VIIa complex can activate factor IX (in addition to factor X). A prolonged PT indicates deficiency of 1 or more coagulation factors (I, II, V, VII, or X) or the presence of a coagulation inhibitor.

The PT is the most common test used for monitoring oral anticoagulant therapy (warfarin or Coumadin, and congeners).Oral anticoagulants reduce the activities of the 4 vitamin K-dependent procoagulant factors (factors II, VII, IX, and X), and the PT is sensitive to 3 of them.

The PT requires standardization because there are numerous thromboplastins and coagulation testing instruments, and they all vary in their responsiveness to the concentrations or activities of coagulation proteins. The international normalized ratio (INR) is a method of standardizing PT reporting for monitoring the intensity of oral anticoagulant therapy. The INR is the ratio of the patient's PT to the laboratoryâ€™s mean normal (reference) PT. The international sensitivity index (ISI) is an experimentally derived measurement, usually provided by the thromboplastin manufacturer, reflecting thromboplastin (and PT) sensitivity to coagulation deficiencies. More sensitive thromboplastins have a low ISI (1.0-1.2), whereas less sensitive thromboplastins have a higher ISI (eg, 2.0-3.0). Calculation of the INR is as follows:

The prothrombin time (PT) test varies in its sensitivity to the activity of coagulation factors II, V, VII, and X, and is least sensitive to decreased factor II.

Mixing studies with normal plasma (ie, adding various proportions of normal pooled plasma to patient plasma) are useful in initial evaluation of prolonged PT when the cause of a prolonged PT is unknown (eg, not attributable to known oral anticoagulation or known coagulation factor deficiency):

-Typically an equal volume mixture (1:1) of patient and normal plasma shortens the prolonged PT into the normal (reference) range when there is a deficiency of 1 or more of the clotting factors (I, II, V, VII, X). Failure to normalize the PT in 1:1 mixing suggests presence of an inhibitor (eg, specific factor inhibitor, lupuslike anticoagulant or antiphospholipid antibody, nonspecific inhibitor).

-Typically the addition of patient plasma of 1/10 or 2/10 volume of normal plasma shortens the prolonged PT, at least halfway toward the upper normal range, when there is a deficiency of 1 or more relevant coagulation factors. Inhibition is implied by failure to significantly shorten the PT.

-Additional coagulation testing may be needed to define the cause of an unexplained prolonged PT (eg, other clotting time tests, coagulation factor assays, testing for presence of a lupuslike anticoagulant). Mixing studies and such additional testing may be included in consultative testing (Coagulation Consultation).

Not useful for detecting deficiencies of coagulation factors that have no influence on the prothrombin time (PT) test (eg, factors VIII, IX, XI, XII, XIII). International normalized ratio (INR) reporting of the PT is useful only for monitoring intensity of stable oral anticoagulant therapy. The activity of coagulation factor V (labile factor) typically may be 10% to 20% lower in frozen-thawed plasma specimens than in fresh specimens, even under optimum conditions of processing and transportation, or may be even lower if these conditions are suboptimal, and may lead to a falsely prolonged PT.

In an occasional individual, a more marked decrease of factor V activity may occur with freeze-thaw of plasma. Hence, the PT of frozen-thawed plasma potentially may be slightly more prolonged than would be observed in testing of fresh specimen. Frozen plasma kept on dry ice (solid carbon dioxide) in closed shipping containers may have spurious prolongation of PT, due to acidification of plasma by absorbed carbon dioxide. Exposure of thawed plasma to a normal atmosphere for a few minutes usually eliminates this spurious effect.

The PT is much less sensitive to heparin effect than is the activated partial thromboplastin time (APTT), and therapeutic concentrations of heparin usually cause only slight prolongation of the PT (< or =1 sec with normal plasma, thromboplastin ISI 1.0, heparin < or =1 microgram/mL).